Untitled

Abstract

In membrane proteins, the extent to which polarity, hydrogen bonding, and van der Waals packing interactions of the buried, internal residues direct protein folding and association of transmembrane segments is poorly understood. The energetics associated with these various interactions should differ substantially between membrane versus water-soluble proteins. To help evaluate these energetics, we have altered a water-soluble, two-stranded coiled-coil peptide to render its sequence soluble in membranes. The membrane-soluble peptide associates in a monomer-dimer-trimer equilibrium, in which the trimer predominates at the highest peptide/detergent ratios. The oligomers are stabilized by a buried Asn side chain. Mutation of this Asn to Val essentially eliminates oligomerization of the membrane-soluble peptide. Thus, within a membrane-like environment, interactions involving a polar Asn side chain provide a strong thermodynamic driving force for membrane helix association.

Structural basis for tetraspanin functions as revealed by the cryo-EM structure of uroplakin complexes at 6-Å resolution

“…It has been proposed that residues mediating interhelical contacts would be more evolutionarily conserved than those that face the lipids because mutations of the former are more likely to destabilize the protein (Donnelly et al, 1993; Stevens and Arkin, 2001; Beuming and Weinstein, 2004). Hence, these conserved polar/charged residues are likely involved in the interhelical interactions in tetraspanin TMs (Choma et al, 2000; F.X. Zhou et al, 2000, 2001).…”

Toll‐like receptor 3 transmembrane domain is able to perform various homotypic interactions: An NMR structural study

“…It includes unusually large quantity of aromatic residues -6 Phe and Trp and a cluster of relatively polar residues (Asn 709 Thr 710 Ser 711 ) deep inside the membrane. It is well-known that highly polar residues in TM helices can drive their association [41,42], and slightly polar residues, such as Gly, Ser, Thr and Ala can mediate the TM helix-helix interactions if they are put together in special motifs, such as GxxxG or ''heptad-repeat'' [43,44]. Aromatic sidechains also bear partial charges and can engage in electrostatic interactions with other aromatic residues or polar sidechains, thus stabilizing the dimerization/oligomerization of TM segments [45].…”

Potential of mean force analysis of the self-association of leucine-rich transmembrane α-helices: Difference between atomistic and coarse-grained simulations

“…[1][2][3] Interactions among TM helices embedded in lipid membranes have been extensively studied in the fields of experimental biochemistry, 2-9 computational chemistry, and theoretical chemistry, aiming to understand the mechanisms, and thermodynamics of the association process of TM helices. [10][11][12][13][14] The association of TM helices in membrane proteins is likely to be controlled by several factors that act in concert, such as surface complementarity, polar residues enabling hydrogen bond formation and/or dipole interactions, 7,15 and certain specific motifs, such as the GxxxG motif. 16 On the other hand, analyses using TM peptides with simple sequences showed robust association of helices, even without specific recognition motifs.…”